Core C: Digital Image Processing The goals of the Digital Image Processing Core are to continue provide analytic tools for all projects. These unique image analysis tools are necessary for unbiased, accurate, quantitative analysis of temporal volumetric changes in single and multimodal MRI data sets of lab animals and human patients. Currently all MRI acquisitions independent of weightings for all interval exams of both animal and human studies are fully automatically registered to a "reference" data set in the first exam typically using a rotate- translate geometry model;this is a multimodality registration problem using existing software tools. Typically a T1-weighted, post-Gad sequence, is used as the reference for registering all successive interval exam sets. B1-field corrections have been found to be unnecessary thus far. In cases where the acquisitions involve high gradient fields such as those used for diffusion or perfusion weighted imaging, registrations are accomplished using a full affine model to support correction of shears caused by the gradients. Currently all human scan data including both original acquisitions and registered datasets, as well as animal backups, are stored on the Core's disk system. In the future all animal scans will be likewise stored on the Core's disks which can be accessed via TCP/IP or SAMBA protocols over 100 Mb ethernet. Of course the Core is responsible for maintaining data integrity and backup. The core will also develop the ability to track the positions of voxels within treated lesions across interval exams using high degree of freedom warpings. This facility for both animal and human imaging will support further investigation of the role of the apparent diffusion coefficient (ADC) as well as other parameters, e.g. perfusion, as potentially early indicators of therapeutic response. Additionally in the A1 amendment this Core demonstrated the ability to map histology back to in vivo MRI voxels for animals (where whole head ex vivo MRI acquisitions are possible) using only intrinsic scan information (i.e. no implanted fiducials of any kind). Pub. Health: Overall, this research effort willprovide therationale for initiation of clinical trials with combinations of molecularly targeted therapies for the treatment of malignant brain tumors. In addition, imaging biomarkers for early assessment of treatment response will be identified and validated which will lead to individualization of patient treatment. University of Michigan Ann Arbor, Michigan PHS 398(Rev. 09/04) Page 3/V Form Page 2 Principal Investigator/Program Director (Last, First, Middle): ROSS, Brian D. KEY PERSONNEL. See instructions. Usecontinuation pages as needed to provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last name first. Name eRA Commons User Name Organization Role on Project Meyer, Charles Cmeyer University of Michigan Core Director Bland, Peyton University of Michigan Co-Investigator OTHER SIGNIFICANT CONTRIBUTORS Name Organization Role on Project Human Embryonic Stem Cells ^ No [~1 Yes If the proposed project involves human embryonic stem cells, list below the registration number of the specific cell llne(s) from the following list: http://stemcells.nih.gov/reaistrv/index.asp. Usecontinuationpages asneeded. If a specific line cannot be referenced at thistime, includea statement that one from the Registry will be used. Cell Line Disclosure Permission Statement Applicable toSBIR/STTR Onlv. See SBIR/STTR instructions. Q Yes Q No PHS 398 (Rev. 09/04) Page 31$" Form Page 2-continued Number the following pages consecutively throughout the application. Do not use suffixes such as 4a, 4b. Principal Investigator/Program Director (Last, first, middle): DETAILED BUDGET FOR INITIAL BUDGET PERIOD DIRECT COSTS ONLY Meyer/Core C PERSONNEL (Applicant organization only) % TYPE EFFORT INST. ROLE ON APPT. ON BASE NAME PROJECT (months) PROJ. SALARY Core Meyer, Charles Director 12 15% $160,680 Co-lnv. Bland, Peyton 12 25% $95,790 System Laderach, Gary Administrator 12 5% $71,028 Programmer Geng, Hairong Analyst 12 100% $53,250 Programmer (TBN) Technical 12 100% $50,000 GSRA Eng. GSRA (TBN) 12 100% $23,422 SUBTOT0.1 " "^ CONSULTANT COSTS EQUIPMENT (Itemize) Purchased in Years 2 &3 SUPPLIES (Itemize bycategory) Mag Tape $500 TRAVEL 1 -2 Trips/year for Core Director PATIENT CARE COSTS INPATIENT OUTPATIENT ALTERATIONS AND RENOVATIONS (Itemize bycategory) OTHER EXPENSES (Itemize bycategory) GSRA Tuition &Fees $14,772 (Fall &Winter) Maintenance Fees $3,000 CONSORTIUM/CONTRACTUAL COSTS Ross, Brian D. FROM THROUGH 12/1/2006 11/30/2007 DOLLAR AMOUNT REQUESTED (omit cents) SALARY FRINGE . REQUESTED BENEFITS TOTALS $24,102 $7,231 $31,333 $23,948 $7,184 $31,132 $3,551 $1,065 $4,616 $53,250 $15,975 $69,225 $50,000 $15,000 $65,000 $23,422 $7,027 $30,449 $178,273 $53,482 $231,755 I $500 $1,200 $17,772 DIRECT COSTS SUBTOTAL DIRECT COSTS FOR INITIAL BUDGET PEF (Item 7a, FacePage) $ 251,227 CONSORTIUM/CONTRACTUAL COSTS | FACILITIES AND ADMINISTRATION COSTS! TOTAL DIRECTCOSTS FOR INITIAL BUDGET PERIOD $ I * 251 ,227 | SBIR/STTR Only: FEE REQUESTED PHS 398 (Rev. 09/04) Page Form Page 4